ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12623000446662

Ethics application status

Approved

Date submitted

17/04/2023

Date registered

2/05/2023

Date last updated

27/07/2023

Date data sharing statement initially provided

2/05/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

A Phase 2 Randomised Controlled Trial of Sodium Selenate as a Disease Modifying Treatment for Chronic Drug-resistant Temporal Lobe Epilepsy - The SeLECT Study

Scientific title

A Phase 2 Randomised Controlled Trial of Sodium Selenate as a Disease Modifying Treatment for Chronic Drug-resistant Temporal Lobe Epilepsy

Secondary ID [1]

None

Universal Trial Number (UTN)

U1111-1291-3258

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Mesial temporal lobe epilepsy

Condition category

Condition code

Neurological

Epilepsy

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Sodium selenate, 15mg three times a day, 26 weeks, oral tablet. Participants will be required to return unused tablets to site each visit to monitor compliance with dosing regimen.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Placebo (microcrystalline cellulose), three times a day, 26 weeks, oral tablet

Control group

Placebo

Outcomes

Primary outcome [1]

Change in desirability of outcome (DOOR) score between active and placebo groups.

The DOOR-epilepsy framework is a consumer co-designed outcome measure combining variables of seizure frequency, adverse events, quality of life, and medication burden into a single score.

Timepoint [1]

Change from baseline to 52 weeks post initiation of treatment.

Secondary outcome [1]

Seizure frequency assessed by diary cards.

Timepoint [1]

Change from baseline to 52 weeks post initiation of treatment.

Secondary outcome [2]

Change in psychiatric comorbidities assessed by the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)

The NDDI-E is a questionnaire designed to screen for depression (including depression severity).

Timepoint [2]

Change from baseline to 52 weeks post initiation of treatment.

Secondary outcome [3]

The anti-seizure medication burden assessed by The Liverpool Adverse Event Profile (LAEP).

The LAEP is a questionnaire used to assess the presence and severity of common adverse effects associated with anti-seizure medications.

Timepoint [3]

Change from baseline to 52 weeks post initiation of treatment.

Secondary outcome [4]

Change in global cognitive function assessed by the Australian Epilepsy Project (AEP) cognitive battery. The AEP cognitive battery is a series of cognitive tests that are specifically designed to assess cognitive deficits that are common in patients with epilepsy.

Timepoint [4]

Change from baseline to 52 weeks post initiation of treatment.

Secondary outcome [5]

Change in quality of life assessed by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31).

The QOLIE-31 is an assessment tool designed to evaluate various health concepts associated with epilepsy, such as emotional well-being, seizure-related concerns, energy and fatigue, cognitive function, medication effects, and overall quality of life.

Timepoint [5]

Change from baseline to 52 weeks post initiation of treatment.

Secondary outcome [6]

Safety will be assessed based on the frequency and severity of adverse events (AEs) as measured by diary cards and face to face report with patients at clinic visits.

Relevant AEs associated with sodium selenate, such as nail changes and hair loss, have been selected for inclusion on the diary cards. Other changes from baseline will be monitored in clinic by reviewing medical history, conducting physical and neurological examinations in accordance with general medical practice, assessing vital signs (including weight using digital scales, blood pressure using a sphygmomanometer, heart rate using a digital heart rate monitor, and temperature using a thermometer), conducting a 12-lead ECG, and analyzing haematology, biochemistry, and urinalysis. Additionally, the Columbia Suicide Severity Rating Scale (C-SSRS) will be used to detect suicidal ideation or suicidal behaviour. All adverse events will be assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAE).

Timepoint [6]

Cumulative from baseline to week 52 post-initiation of treatment.

Secondary outcome [7]

Change in psychiatric comorbidities assessed by the General Anxiety Disorder-7 (GAD-7).

The GAD-7 is a questionnaire designed to screen for anxiety.

Timepoint [7]

Change from baseline to 52 weeks post initiation of treatment.

Secondary outcome [8]

Timepoint [8]

Change from baseline to 26 weeks post initiation of treatment.

Secondary outcome [9]

Seizure frequency assessed by diary cards.

Timepoint [9]

Change from baseline to 26 weeks post initiation of treatment.

Secondary outcome [10]

Timepoint [10]

Change from baseline to 26 weeks post initiation of treatment.

Secondary outcome [11]

Timepoint [11]

Change from baseline to 26 weeks post initiation of treatment.

Secondary outcome [12]

Timepoint [12]

Change from baseline to 26 weeks post initiation of treatment.

Secondary outcome [13]

Change in psychiatric comorbidities assessed by the General Anxiety Disorder-7 (GAD-7)

The GAD-7 is a questionnaire designed to screen for anxiety.

Timepoint [13]

Change from baseline to 26 weeks post initiation of treatment.

Secondary outcome [14]

Epileptiform discharge assessed by ambulatory 24 hour EEG recording.

Timepoint [14]

Change from baseline to 52 weeks post initiation of treatment.

Secondary outcome [15]

Epileptiform discharge assessed by ambulatory 24 hour EEG recording.

Timepoint [15]

Change from baseline to 26 weeks post initiation of treatment.

Secondary outcome [16]

Tolerability will be assessed by measure of withdrawal rates from the study by an audit of study records.

Timepoint [16]

Cumulative from baseline to week 52 post-initiation of treatment.

Eligibility

Key inclusion criteria

1. Male or female (aged 18-75 years).
2 Subjects must have a diagnosis of drug-resistant temporal lobe epilepsy (TLE) for at least 2 years at the time of screening.
3. Participants must have 4 or more countable seizures per month (any combination of focal impaired awareness seizures, focal to bilateral tonic clonic seizures or focal aware seizures with motor symptoms)
4. Participants must be on 1 or more stable ASM for a period of >8 weeks
5. Participants must have interictal epileptiform discharges (average >1 spike/hr) on baseline 24-hour EEG localising to one or both temporal lobes without extratemporal discharges or seizures
6. All participants of reproductive potential must be using effective contraception for the duration of the trial and for 4 weeks following cessation of the investigational medicinal product (IMP). Female participants of non-childbearing potential must be either surgically sterile (hysterectomy and/or oophorectomy) or postmenopausal at least 1 year. All female participants must have a negative plasma hCG pregnancy test at screening.

Minimum age

18 Years

Maximum age

75 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Participants with extra-temporal or genetic generalised epilepsy
2 Current or historic substance use disorder (as per DSM V criteria).
2. Women who are pregnant or lactating and persons of reproductive potential unwilling/unable to take adequate contraceptive precaution for the duration of the study are excluded.
3. Participants who have recently (within 3 months of screening) participated in another interventional clinical trial are excluded.
4. Participants who have recent (within 5 years) history of psychogenic non-epileptic seizures, or who have significant medical or neurological disease other than epilepsy that is not adequately controlled by therapy are excluded.
5. Participants who have commenced medications with a known effect on mood, cognition or seizures within 4 weeks of screening are also excluded.
6. Participants with a known sensitivity to selenium, sodium selenate, any medicine or vitamin containing sodium selenate, similar agents or any of the excipients (including microcrystalline cellulose) used are excluded.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Allocation involves contacting the holder of the allocation schedule who was "off-site" or at central administration site.
(central randomisation by phone/fax/computer)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation using a randomisation table created by computer software

Participants will be stratified based on their seizure frequency during the screening period (greater or fewer than 8 seizures/month) and the presence or absence of hippocampal/mesial temporal sclerosis.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 2

Type of endpoint/s

Efficacy

Statistical methods / analysis

Statistical power has thus been determined on the primary outcome variable (change in DOOR scale score). A sample size of 108 patients would yield power of 0.8 to observe such hypothesized treatment effect against the null hypothesis of no treatment effect (Win Ratio greater than or equal to 1) assuming two-sided alpha level of 0.05. In order to account for 10-15% potential losses due to screen failures and non-evaluable data the final sample size for this study is set as 124 participants.

Secondary endpoints will utilise generalised linear models (GLMs) to assess group level differences between baseline and week 26 to assess anti-seizure effects, and baseline and week 52 to assess anti-epileptogenesis effects. Differences in seizure frequency on seizure diaries, epileptiform discharge frequency on 24 hour EEGs, NDDI-E score, GAD-7 score, QOLIE-31 score, NIH toolbox composite score, LAEP score will all be compared between treatment and placebo groups. Baseline measures will be included in the models as covariates and the model will estimate the adjusted mean change (with 95% confidence intervals) as a marker of treatment.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/10/2023

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

124

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,WA,VIC

Recruitment hospital [1]

The Alfred - Melbourne

Recruitment hospital [2]

Royal Melbourne Hospital - City campus - Parkville

Recruitment hospital [3]

Austin Health - Austin Hospital - Heidelberg

Recruitment hospital [4]

Eastern Health - Box Hill

Recruitment hospital [5]

St Vincent's Hospital (Melbourne) Ltd - Fitzroy

Recruitment hospital [6]

Royal Brisbane & Womens Hospital - Herston

Recruitment hospital [7]

Mater Adult Hospital - South Brisbane

Recruitment hospital [8]

Sir Charles Gairdner Hospital - Nedlands

Recruitment hospital [9]

Westmead Hospital - Westmead

Recruitment postcode(s) [1]

3004 - Melbourne

Recruitment postcode(s) [2]

3050 - Parkville

Recruitment postcode(s) [3]

3084 - Heidelberg

Recruitment postcode(s) [4]

3128 - Box Hill

Recruitment postcode(s) [5]

3065 - Fitzroy

Recruitment postcode(s) [6]

4029 - Herston

Recruitment postcode(s) [7]

4101 - South Brisbane

Recruitment postcode(s) [8]

6009 - Nedlands

Recruitment postcode(s) [9]

2145 - Westmead

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

NHMRC (MRFF)

Address [1]

16 Marcus Clarke St,
Canberra ACT 2601

Country [1]

Australia

Primary sponsor type

Hospital

Name

Alfred Health

Address

55 Commercial Road
Melbourne
3004 VIC

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Alfred Health HREC

Ethics committee address [1]

55 Commercial Road
Melbourne
VIC 3004

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

22/05/2023

Approval date [1]

11/07/2023

Ethics approval number [1]

Summary

Brief summary

This study will investigate a new drug, sodium selenate, for the treatment of drug-resistant temporal lobe epilepsy (TLE). Up to 124 patients with TLE will be recruited in to the study. Half of the patients will receive 26 weeks of treatment with sodium selenate (15 mg three times a day), and the other half a placebo (a sugar pill). The primary outcome will be the a consumer co-designed DOOR-epilepsy rank, combining change in seizure frequency, adverse events, quality of life and ASM burden measures into a single outcome measure, compared between treatment and placebo groups over the whole 52 week period. Secondary outcomes include measures of seizures, epileptiform activity, cognitive and, neuropsychiatric outcome measures, quality of life, and medication burden at the end of 26 and 52 weeks (compared to baseline). Other measures will include safety and tolerability and exploratory biomarkers of treatment response.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Terence O'Brien

Address

Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC

Country

Australia

Phone

+61418370566

Fax

[email protected]

Contact person for public queries

Name

Lucy Vivash

Address

Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC

Country

Australia

Phone

+61 3 9903 0860

Fax

[email protected]

Contact person for scientific queries

Name

Lucy Vivash

Address

Level 6, The Alfred Centre
99 Commercial Road
Melbourne
3004 VIC

Country

Australia

Phone

+61 3 9903 0860

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

All deidentified trial data will be publicly available, after publication of study results.
Additionally - biospecimens will be available to genuine researchers upon request (and justification) to the study team

When will data be available (start and end dates)?

Immediately following publication of study results, no end date

Available to whom?

Deidentified trial data will be publically available to anyone who wishes to access it.
Biospecimen data will be made available to researchers who supply a proposal to the study team/ lead HREC. Not all biospecimen data will be freely available due to participants being given the option of specified/extended/unspecified consent for the long-term use of these data.

Available for what types of analyses?

Main trial data will be available for any types of analyses.
Biospecimen data will be given to achieve the aims of submitted proposals in alignment with any restrictions placed on future use of data

How or where can data be obtained?

Upon direct request to the study team (see contact information page for phone/emails of PI and PM) a summary of available data will be made available on the Monash University Website.
PI: [email protected]
PM: [email protected]

What supporting documents are/will be available?

Doc. No.	Type	Email	Other Details
18875	Study protocol	[email protected]
18876	Statistical analysis plan	[email protected]
18877	Informed consent form		To be supplied upon HREC approval
18878	Ethical approval		To be supplied upon HREC approval

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

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Documents added automatically